全文获取类型
收费全文 | 8093篇 |
免费 | 532篇 |
国内免费 | 4篇 |
出版年
2024年 | 7篇 |
2023年 | 18篇 |
2022年 | 49篇 |
2021年 | 157篇 |
2020年 | 87篇 |
2019年 | 119篇 |
2018年 | 163篇 |
2017年 | 156篇 |
2016年 | 226篇 |
2015年 | 429篇 |
2014年 | 432篇 |
2013年 | 512篇 |
2012年 | 720篇 |
2011年 | 625篇 |
2010年 | 398篇 |
2009年 | 366篇 |
2008年 | 484篇 |
2007年 | 508篇 |
2006年 | 454篇 |
2005年 | 392篇 |
2004年 | 384篇 |
2003年 | 325篇 |
2002年 | 285篇 |
2001年 | 249篇 |
2000年 | 230篇 |
1999年 | 165篇 |
1998年 | 62篇 |
1997年 | 54篇 |
1996年 | 34篇 |
1995年 | 34篇 |
1994年 | 21篇 |
1993年 | 21篇 |
1992年 | 40篇 |
1991年 | 48篇 |
1990年 | 39篇 |
1989年 | 46篇 |
1988年 | 35篇 |
1987年 | 25篇 |
1986年 | 25篇 |
1985年 | 31篇 |
1984年 | 20篇 |
1983年 | 17篇 |
1981年 | 9篇 |
1979年 | 11篇 |
1978年 | 13篇 |
1977年 | 10篇 |
1974年 | 12篇 |
1973年 | 14篇 |
1972年 | 11篇 |
1971年 | 7篇 |
排序方式: 共有8629条查询结果,搜索用时 296 毫秒
101.
Sunkyu Choi Kun Cho Kyungmoo Yea Jeonghwa Lee Jeongkwon Kim 《Biochemical and biophysical research communications》2009,383(1):135-140
Hypoxia during the expansion of adipocytes is known to contribute both to the secretion of multiple inflammation-related adipokines as well as to obesity. We therefore investigated the nature of protein changes occurring in adipocytes during hypoxia by observation of the intracellular proteins that are expressed in 3T3-L1 adipocytes. Lysates were utilized for quantitative proteome analysis using isobaric tags for relative and absolute quantitation (iTRAQ) combined with peptide separation by multi-dimensional liquid chromatography. Antioxidants and elongation factors, as well as glycolytic enzymes were increased in hypoxic adipocytes. These changes were supported by similar changes suggested by real-time PCR. The proteins showing changes are all potential targets for revering the mechanism behind the phenomenon of induction of obese adipocytes by hypoxia. This study can therefore aid in defining the proteomic changes that occur in adipocytes in response to oxygen stress, and can further characterize adipocyte metabolism and adaptation to low oxygen conditions. 相似文献
102.
103.
Hyo Je Cho Kyungsun Kim Seo Yean Sohn Ha Yeon Cho Kyung Jin Kim Myung Hee Kim Dockyu Kim Eungbin Kim Beom Sik Kang 《The Journal of biological chemistry》2010,285(45):34643-34652
A meta-cleavage pathway for the aerobic degradation of aromatic hydrocarbons is catalyzed by extradiol dioxygenases via a two-step mechanism: catechol substrate binding and dioxygen incorporation. The binding of substrate triggers the release of water, thereby opening a coordination site for molecular oxygen. The crystal structures of AkbC, a type I extradiol dioxygenase, and the enzyme substrate (3-methylcatechol) complex revealed the substrate binding process of extradiol dioxygenase. AkbC is composed of an N-domain and an active C-domain, which contains iron coordinated by a 2-His-1-carboxylate facial triad motif. The C-domain includes a β-hairpin structure and a C-terminal tail. In substrate-bound AkbC, 3-methylcatechol interacts with the iron via a single hydroxyl group, which represents an intermediate stage in the substrate binding process. Structure-based mutagenesis revealed that the C-terminal tail and β-hairpin form part of the substrate binding pocket that is responsible for substrate specificity by blocking substrate entry. Once a substrate enters the active site, these structural elements also play a role in the correct positioning of the substrate. Based on the results presented here, a putative substrate binding mechanism is proposed. 相似文献
104.
Joomin Lee Haeun Song Kangsan Roh Sungrae Cho Sukchan Lee Chang‐Hwan Yeom Seyeon Park 《Cell biochemistry and function》2016,34(5):317-325
The lymphatic vascular system plays an important role in tissue fluid homeostasis. Lymphedema is a chronic, progressive, and incurable condition that leads to lymphatic fluid retention; it may be primary (heritable) or secondary (acquired) in nature. Although there is a growing understanding of lymphedema, methods for the prevention and treatment of lymphedema are still limited. In this study, we investigated differential protein expressions in sham‐operated and lymphedema‐operated mice for 3 days, using two‐dimensional gel electrophoresis (2‐DE) and mass spectrometry analysis. Male improved methodology for culturing noninbred (ICR) mice developed lymphedema in the right hindlimb. Twenty functional proteins were found to be differentially expressed between lymphedema induced‐right leg tissue and normal left leg tissue. Out of these proteins, the protein levels of apolipoprotein A‐1 preprotein, alpha‐actinin‐3, mCG21744, parkinson disease, serum amyloid P‐component precursor, annexin A8, mKIAA0098 protein, and fibrinogen beta chain precursor were differentially upregulated in the lymphedema mice compared with the sham‐operated group. Western blotting analysis was used to validate the proteomics results. Our results showing differential up‐regulation of serum amyloid P‐component precursor, parkinson disease, and apolipoprotein A‐1 preprotein in lymphedema model over sham‐operated model suggest important insights into pathophysiological target for lymphedema. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
105.
106.
Effect of abscisic acid application on root isoflavonoid concentration and nodulation of wild-type and nodulation-mutant soybean plants 总被引:1,自引:0,他引:1
Isoflavonoids (daidzein, genistein, and coumestrol) are involved in induction of nod genes in Bradyrhizobium japonicum and may be involved in nodule development as well. Abscisic acid (ABA) may also impact nodulation since ABA is reportedly
involved in isoflavonoid synthesis. The current study was conducted to evaluate whether ABA plays a role in differential nodulation
of a hypernodulated soybean (Glycine max L. Merr.) mutant and the Williams parent. Exogenous ABA application resulted in a decrease in nodule number and weight in
both lines. Isoflavonoid concentrations were also markedly decreased in response to ABA application in both inoculated and
noninoculated soybean roots. The inoculation treatment itself resulted in a marked increase in isoflavonoid concentrations
of NOD1-3, regardless of ABA levels, while only slight increases occurred in Williams. The nodule numbers of both soybean
lines across several ABA concentration treatments were highly correlated with the concentration of all three isoflavonoids.
However, differences in internal levels of ABA between lines were not detected when grown in the absence of external ABA additions.
It is concluded that differential nodule expression between the wild type and the hypernodulated mutant is not likely due
to differential ABA synthesis. 相似文献
107.
108.
Anne Durand Fabien Chauveau Tae-Hee Cho Radu Bolbos Jean-Baptiste Langlois Laure Hermitte Marlène Wiart Yves Berthezène Norbert Nighoghossian 《PloS one》2012,7(11)
Injection of thrombin into the middle cerebral artery (MCA) of mice has been proposed as a new model of thromboembolic stroke. The present study used sequential multiparametric Magnetic Resonance Imaging (MRI), including Magnetic Resonance Angiography (MRA), Diffusion-Weighted Imaging (DWI) and Perfusion-Weighted Imaging (PWI), to document MCA occlusion, PWI-DWI mismatch, and lesion development. In the first experiment, complete MCA occlusion and reproducible hypoperfusion were obtained in 85% of animals during the first hour after stroke onset. In the second experiment, 80% of animals showed partial to complete reperfusion during a three-hour follow-up. Spontaneous reperfusion thus contributed to the variability in ischemic volume in this model. The study confirmed the value of the model for evaluating new thrombolytic treatments, but calls for extended MRI follow-up at the acute stage in therapeutic studies. 相似文献
109.
110.
Yong-Bin Cho Sungguan Hong Kyung-Won Kang Ji-Hun Kang Sang-Myeong Lee Young-Jin Seo 《Journal of cellular and molecular medicine》2020,24(10):5463-5475
The influenza virus is one of the major public health threats. However, the development of efficient vaccines and therapeutic drugs to combat this virus is greatly limited by its frequent genetic mutations. Because of this, targeting the host factors required for influenza virus replication may be a more effective strategy for inhibiting a broader spectrum of variants. Here, we demonstrated that inhibition of a motor protein kinesin family member 18A (KIF18A) suppresses the replication of the influenza A virus (IAV). The expression of KIF18A in host cells was increased following IAV infection. Intriguingly, treatment with the selective and ATP-competitive mitotic kinesin KIF18A inhibitor BTB-1 substantially decreased the expression of viral RNAs and proteins, and the production of infectious viral particles, while overexpression of KIF18A enhanced the replication of IAV. Importantly, BTB-1 treatment attenuated the activation of AKT, p38 MAPK, SAPK and Ran-binding protein 3 (RanBP3), which led to the prevention of the nuclear export of viral ribonucleoprotein complexes. Notably, administration of BTB-1 greatly improved the viability of IAV-infected mice. Collectively, our results unveiled a beneficial role of KIF18A in IAV replication, and thus, KIF18A could be a potential therapeutic target for the control of IAV infection. 相似文献